text: The kinetic isotope effect is considered to be one of the most essential and sensitive tools for the study of reaction mechanisms, the knowledge of which allows the improvement of the desirable qualities of the corresponding reactions. For example, kinetic isotope effects can be used to reveal whether a nucleophilic substitution reaction follows a unimolecular (S1) or bimolecular (S2) pathway.
  In the reaction of methyl bromide and cyanide (shown in the introduction), the observed methyl carbon kinetic isotope effect indicates an S2 mechanism. Depending on the pathway, different strategies may be used to stabilize the transition state of the rate-determining step of the reaction and improve the reaction rate and selectivity, which are important for industrial applications.
  Isotopic rate changes are most pronounced when the relative mass change is greatest, since the effect is related to vibrational frequencies of the affected bonds. For instance, changing a hydrogen atom (H) to its isotope deuterium (D) represents a 100% increase in mass, whereas in replacing carbon-12 with carbon-13, the mass increases by only 8 percent. The rate of a reaction involving a C–H bond is typically 6–10 times faster than the corresponding C–D bond, whereas a C reaction is only 4 percent faster than the corresponding C reaction (even though, in both cases, the isotope is one atomic mass unit heavier).
  Isotopic substitution can modify the rate of reaction in a variety of ways. In many cases, the rate difference can be rationalized by noting that the mass of an atom affects the vibrational frequency of the chemical bond that it forms, even if the potential energy surface for the reaction is nearly identical. Heavier isotopes will (classically) lead to lower vibration frequencies, or, viewed quantum mechanically, will have lower zero-point energy. With a lower zero-point energy, more energy must be supplied to break the bond, resulting in a higher activation energy for bond cleavage, which in turn lowers the measured rate (see, for example, the Arrhenius equation).